Tuesday, March 16, 2021

Secret Science Club Zoom Lecture: The Vulnerable Brain

Tonight, there's a Secret Science Club Zoom lecture featuring neuroscientist Dr Yasmin Hurd, professor of psychiatry, neuroscience and pharmacological sciences at the Icahn School of Medicine at Mount Sinai, director of the Addiction Institute at the Mount Sinai Behavioral Health System, and Ward-Coleman Chair of Translational Neuroscience. Dr Hurd is a member of the Dana Foundation, and this lecture is the annual Brain Awareness Week collaboration between the Dana Foundation and the Secret Science Club. 

Dr Hurd began her lecture with an overview of her topic, pathways to and from addiction. She noted that 30 million Americans have substance use disorders, which pose a trillion dollar problem to the US, reducing the quality of life for many. We are in an epidemic of overdose deaths, placing the healthcare system under siege. She noted that the COVID-19 pandemic has many people affected by stress and social isolation, and substance use disorders are up as a result. Individuals with substance use problems are vulnerable to COVID-19 infection. Addiction is a clinical disorder and the DSM-5 lists 11 characteristics of addiction.

We know a lot about the Nucleus accumbens Amygdala VTA-ventral reward pathways. The drugs that are addictive impact many neurotransmitters- dopamine, glutamate, endogenous opiod and cannabinoid transmitters Nucleus accumbens activation/dopamine Addiction is not a disorder of reward, though reward often kicks it off. it's a disorder of plasticity.

Addiction risk is effected by neurodevelopment, involving such factors as genetics and environmental exposure.  There are genetic and epigenetic factors. Heritability studies indicated that cocaine and opioid addictions have significant genetic underpinnings. Mu opioid receptors mediate the effects of opioids.  A single nucleotide polymorphism in the genome is associated with high risk of opioid use disorder and overdose.

Cannabis use disorder affects 30% of cannabis users, and mimics other substance use disorders- higher negative affect, neurosis, anxiety. Many people consume cannabis without cannabis use disorder, genetics in synergy with negative affect cause disorder. 

Dr Hurd then discussed environmental causes- childhood trauma plays a role in adult addiction risk. A study of cocaine use disorder affected adults with childhood trauma showed prefrontal cortex irregularities. Low dopamine D2 levels can play a role in substance abuse disorders. Social isolation and stress (usually among subordinate status individuals) lowers dopamine D2 levels. The endocannabinoid system plays a critical role in neurodevelopmental processes during childhood and adolescence. 

Dr Hurd posed the question, "What is the role of cannabis in development?" There is a perception that cannabis is largely safe. The cannabinoid receptor in the brain is critical for the hardwiring of the brain, helping neural pathways to grow. In utero cannabis exposure can cause impairments in fetal brain development. What are the long-term consequences on adult behavior? Animal studies show that a decrease in the dopamine D2 receptors in animals exposed in utero to cannabis. Prenatal THC exposure also tends to cause an increase in opioid use among lab animals. Dr Hurd joked that she is a masochist, and her 'even more masochistic' colleague Yoko Nomura decided to study the development of children exposed to cannabis in utero throughout their lifetimes, starting with studies of the mothers' placentas. Young children exposed to cannabis in utero tend to have higher stress hormone (cortisol) levels. Prenatal THC exposure also increase one's desire for reward- for example, subjects will push a button a hundred times for a chocolate. Cannabis exposure changes epigenetic mechanisms, helping to turn or or turn off genetic mechanisms. Epigenetic effects can change brain plasticity, leading to protracted changes in behavior. 

Adolescent cannabis exposure is associated with a greater incidence of other drug use, and can alter behavioral traits, including an increased risk of suicide. Adolescent THC use can reduce the complexity of neurons in the prefrontal cortex. A complete reorganization in the cortical gene profile occurs, linked to changes in epigenetic processes and plasticity. Heroin and cannabis use have similar effects on plasticity. 

Can we use what we learned to find a pathway out of addiction? Glutametergic disregulation and epigenetic disruption correlate to years of heroin use. These changes are very specific, and can be studied in lab animals. Cancer medicines which effect epigenetics can decrease heroin self-administration among lab animals. Perhaps, epigenetic mechanisms can be targeted to reduce heroin use. Cannabis contains 500 chemicals, including 140 cannabinoids. THC is the cannabinoid that gets users high, and is the best studied cannabinoid. Dr Hurd wanted to study cannabidiol CBD, which reduces heroin seeking behavior in lab animals. CBD can also slow the deterioration of plasticity and glutametergic effects. Among heroin abstainers, CBD reduces heroin cravings, it also reduces cue-induced anxiety among heroin abstainers. CBD reduces cortisol levels and heart rates among cue-induced heroin abstainers. Clinical trials are being developed to study CBD. Dr Hurd noted that CBD is being added to everything from ice cream to hamburgers to dog food, and noted that we need to return to a medical approach to determine the utility of CBD to treat addiction. 

The lecture was followed with a Q&A session. The first question involved tobacco use- most cannabis users also smoke tobacco, and the synergy needs to be studied further. A question about Dr Carl Hart's book about responsible adult drug use elicited a response that recreational drug users should be identified early on so that medical treatment should be started... there should not be a stigma about addiction, which should be treated as a medical issue, not a criminal justice issue. Opioid addiction is real and it destroys individuals and families. Asked about cannabis being a 'gateway drug', Dr Hurd noted that lab animals presented with a rich environment are less likely to use heroin- if the choice is 'heroin or nothing', heroin is a likely choice. She noted that people choose to use marijuana because it has a certain effect, but that THC concentration has increased dramatically since the 1970s. As far as CBD being put in everything, Dr Hurd noted that the concentrations are much lower than those used medicinally, but that CBD sources are not regulated, and that adulteration is a potential problem. Regarding gambling or sex addictions, non-chemical addictions, Dr Hurd noted that she has a bias, studying chemical addictions- chemical addictions are much stronger than behavioral addictions, a hit of cocaine is much stronger than hitting a jackpot. Epigenetic changes are associated with behavioral addictions, but more study is needed- there are shared neurobiological conditions involved. Another question involved the utility of studying the genetic polymorphism that leads to increased opioid vulnerability as an adjunct to pain management, to avoid opioid addiction... Dr Hurd indicated that this is a sound policy, and should also be used in determining methadone dosages for recovering heroin addicts. There is no staging of addiction- psychological and social factors should be taken in consideration as well as genetic factors. Dr Hurd noted that she doesn't need a cheek swab to know that a particular patient may be at risk. As far as 'repairing' the brain, epigenetics can be reversed, the changes are not mutations, so they are not permanent. Addiction is not a lifetime damnation, recovery is possible, but there is no grand playbook to bring it about. Dr Hurd noted that opioids are critical therapeutic substances, but the problem is with high-use, high-dose opioids. Smaller doses, perhaps in conjunction with cannabinoids, are preferred therapeutically. Small doses aren't a 'big hammer to the brain'. Some Bastard in the audience asked Dr Hurd to contrast the effects of alcohol with the effects of opioids and cannabinoids- alcohol has a broader effect on the brain, but its effects on plasticity and brain epigenetics can be mitigated with CBD- very few individuals only use one drug.

Kudos to Dr Hurd, Margaret and Dorian, and the fantastic people of the Dana Foundation for providing this fantastic lecture.  For a taste of Dr Hurd's knowledge, here is a video of her lecturing about the neurobiology of addiction:

 Pour yourself a nice beverage, sit back, and soak in that SCIENCE!!!

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